Mechanism of lanthanum inhibition of extracellular ATP-evoked calcium mobilization in MDCK cells.
We have studied the effects of La3+ on ATP-evoked rises in intracellular calcium levels ([Ca2+]i) measured by fura-2 fluorimetry in Madin Darby canine kidney (MDCK) cells. ATP evoked [Ca2+]i rises dose-dependently with an EC50 of 2.5 microM. The trigger for the Ca2+ signal was a release of Ca2+ from the inositol-1,4,5-trisphosphate (IP3)-sensitive stores because the signal was completely blocked by pretreatment with the endoplasmic reticulum (ER) Ca2+ pump inhibitor thapsigargin (TG) or the phospholipase C (PLC) inhibitor U73122. Both the peak height and area under the curve of 10 microM ATP-evoked Ca2+ signal was reduced by approximately 50% by extracellular Ca2+ removal, suggesting that ATP induced capacitative Ca2+ entry. La3+ inhibited the ATP-evoked Ca2+ signal dose-dependently when added before or after ATP. Pretreatment of 0.1 mM La3+ inhibited approximately 90% of the Ca2+ signal induced by 10 microM ATP. The mechanisms underlying the La3+ inhibition appear to involve not only block of capacitative Ca2+ entry but also interference with ATP binding to the ATP receptors.
Jan
C R
CR
Department of Medical Education and Research, Veterans General Hospital-Kaohsiung, National Sun Yat-Sen University, Taiwan, ROC. crjan@isca.vghks.gov.tw
Ho
C M
CM
Wu
S N
SN
Huang
J K
JK
Tseng
C J
CJ
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology*
D007811:Lanthanum; D000255:Adenosine Triphosphate; D002118:Calcium